A large number of medical conditions can directly affect the heart including heart failure, abnormal blood pressure, pregnancy, and trauma. Cardiac data can provide information on the progression of a disease or injury affecting a patient. The ability to safely, easily, and accurately measure cardiac function will provide the healthcare professional with critical information needed to provide appropriate and timely care. A system that enables a reliable measurement of cardiac data is therefore critical in the provision of effective health care. Both qualitative and quantitative aspects of cardiac function need to be monitored to assess, diagnose and treat problematic cardiac symptoms. In particular, stroke volume, cardiac output, and ejection fraction are important parameters commonly measured to aid a physician in determining a patient's state of cardiac health and uncover other conditions that might affect cardiac health.
Definition of Key Cardiac Functional Metrics:
Stroke volume is defined as the amount of blood pumped by the left ventricle of the heart in one contraction. Stroke volume is calculated by subtracting the left ventricle diastolic volume from the left ventricle systolic volume. The heart does not pump all the blood out of the ventricle with each contraction. In healthy individuals, only about two-thirds of the blood in the ventricle is displaced and pumped out with each heartbeat. For example, if the left ventricle diastolic volume is 125 ml and the left ventricle systolic volume is 55 ml, the stroke volume is 70 ml.
Cardiac output is defined as the volume of blood pumped by the heart over a fixed period of time. Typically, cardiac output is expressed as the volume of blood pumped by the left ventricle in one minute. Cardiac output is calculated by multiplying the stroke volume by the heart rate. For example, if there are 70 beats per minute and 70 ml of blood is ejected with each beat of the heart, the cardiac output is 4900 ml/minute. This value is typical for an average adult at rest, although cardiac output may reach up to 30 liters/minute during extreme exercise.
Ejection fraction is defined as the ratio of the volume of blood pumped by the heart with respect to the maximum volume of the heart. Specifically, ejection fraction is calculated by dividing the left ventricle stroke volume by the left ventricle diastolic volume. For example, if 70 ml of blood is ejected with each beat of the heart and the diastolic LV volume is 125 ml, the corresponding ejection fraction is 56%. Ejection fraction provides a measure of the heart's pumping efficiency with ratios in the 50% to 60% range being normal for healthy adults while ratios below 35% are an indicator of serious cardiovascular problems.
Examples of Medical Conditions Affecting Cardiac Function:
Heart failure is a disorder in which the heart pumps blood inadequately, leading to reduced blood flow, back up and congestion of blood in the veins and lungs, and other changes that may further weaken the heart, eventually leading to death. Changes in cardiac function associated with heart failure result in a decrease in cardiac output. Decreased cardiac output is caused by a decline in stroke volume that is due to systolic dysfunction, diastolic dysfunction, or a combination of the two. Systolic dysfunction results from a loss of intrinsic inotropy or contractility, most likely due to alterations in signal transduction mechanisms responsible for regulating inotropy. Global systolic dysfunction can also result from the loss of viable, contracting muscle as occurs following acute myocardial infarction. Diastolic dysfunction refers to the diastolic properties of the ventricle and occurs when the ventricle becomes less compliant or stiffer, which impairs ventricular filling. Both systolic and diastolic dysfunctions produce a higher ventricular end-diastolic pressure, which serves as a compensatory mechanism to augment stroke volume according to the Frank-Starling mechanism. The Frank-Starling mechanism describes the ability of the heart to change its force of contraction and therefore stroke volume in response to changes in venous return. In some types of heart failure, such as dilated cardiomyopathy, the ventricle dilates as preload pressures increase to recruit the Frank-Starling mechanism in an attempt to maintain normal stroke volumes.
High blood pressure is another negative medical condition related to poor cardiac function. High blood pressure with no known cause is called primary or essential hypertension. Estimates suggest between 85% and 90% of people with high blood pressure have primary hypertension. Several factors, including changes in the heart and blood vessels probably combine to increase blood pressure. For instance, cardiac output may be increased and the resistance to blood flow may be increased because blood vessels are constricted, causing higher blood pressure. Additionally, a subject's blood volume may also be increased which will also increase blood pressure. The reasons for such changes are not fully understood but appear to involve an inherited abnormality affecting the constriction of arterioles, which help control blood pressure.
Contrarily, low blood pressure is another negative condition related to poor cardiac function. Various disorders and drugs can result in low blood pressure. For example, cardiac output may be reduced as a result of heart disease, such as a heart attack (myocardial infarction), a heart valve disorder, an extremely rapid heartbeat (tachycardia), a very slow heartbeat (bradycardia), or other abnormal heart rhythm (arrhythmia).
Cardiac function during pregnancy is an important indicator of both fetal and maternal health. During pregnancy, the mother's heart must work harder because as the fetus grows, the heart must pump more blood to the uterus. By the end of pregnancy, the uterus is receiving approximately one-fifth of the mother's blood supply. During pregnancy, the mother's cardiac output increases by 30 to 50%. As cardiac output increases, the mother's resting heart rate speeds up from a normal pre-pregnancy rate of about 70 beats per minute to 80 or 90 beats per minute. During exercise, cardiac output and heart rate increase more when a woman is pregnant than when she is not. During labor, cardiac output increases by an additional 10%. After delivery, cardiac output decreases rapidly at first, then more slowly, returning to the mother's pre-pregnancy level about six weeks after delivery. Various complications during pregnancy manifest themselves through changes in cardiac function. For example, cardiac output is significantly elevated in a preclinical state of pre-eclampsia, a serious condition exhibited by an attack of convulsions that can lead to coma, seizures, and death. Consequently, the capability to track a mother's and her fetus's cardiac function during pregnancy can provide critical information to enhance care and outcomes.
Cardiac functional measurement is a critical parameter to track in many circumstances, including emergency situations. For example, hemorrhage, profuse and uncontrollable bleeding, is the primary cause of death on the battlefield and a leading cause of death in civilian trauma. Under conditions of hemorrhage, the stimuli for cardiovascular compensation are similar: both decrease venous return and preload, resulting in both decreased stroke volume and cardiac output. The reduction of stroke volume during hemorrhage reflects the degree of blood loss, but accurate assessment of stroke volume during emergency situations in the field is currently not possible. Hence, it would be beneficial if emergency response personnel were provided with portable devices to track stroke volume.
Current Diagnostic Techniques:
The need for reliable real-time, non-invasive monitoring and measurement of stroke volume, cardiac output, and ejection fraction is considerable. Current devices and techniques suffer from several serious limitations, including but not limited to: extreme and risky invasive application, the need for direct attachment of devices to the subject, complicated operation and/or interpretation allowing only skilled individuals to effectively use the devices, exposure to exceptionally hazardous ionizing radiation, large and bulky systems which prevent mobility and flexible utility in field settings, and, among others, defeat by physical barriers. These drawbacks greatly limit their applicability to, at best, controlled clinical settings, depriving the overall population of important medical information. Effective, mobile systems that can easily be used by a responder are not available.
Following are brief descriptions of current devices and techniques used to monitor cardiac function. One of the most frequently used, an electrocardiogram, generally known as an ECG or EKG, is a test that records the heart's electrical activity using electrodes attached to the surface of the chest. Cardiac data is obtained by measuring the surface electrical signals emanating from the conductive cells of the heart during the cardiac cycle. Measurement of the electrical signals transmitted by the cardiac nerves and propagated through the heart muscle provides an indirect indication, rather than a direct indication, of the mechanical function of the heart. A significant problem associated with an ECG is that electrical signals do not necessarily give a direct indication of the heart's actual pumping status. For example, electrical signals can still be measured and reported by an ECG device when the heart is actually in mechanical standstill and no blood is flowing. This false positive, pulse less electrically activity, can obviously lead to confusion for the caregiver or emergency responder, potentially causing inappropriate treatment.
Merely sensing that the heart is beating electrically still may not provide sufficient information to determine whether the left and right ventricles are actually contracting, and thus outputting blood, Further, using traditional ECG-based methods, it can be difficult to determine whether each of the ventricles are in fact contracting in unison and thereby evenly distributing blood. The ability to monitor the mechanical motion of the ventricles would provide significant additional information to accurately assess cardiac function.
Echocardiography is a second technology commonly used to collect cardiac data. It involves the use of low power, high frequency ultrasound waves, which are directed at the heart by placing a transducer covered in conductive gel directly on the surface of the chest and aiming the transducer at the heart. Echocardiography is generally suitable only for single batch measurement and cannot be easily adapted for continuous or instantaneous monitoring. Echocardiography can be used to obtain limited two-dimensional imaging of the left ventricle to provide estimates of cardiac chamber volume, which in turn allow rough calculation of estimated ejection fraction, stroke volume and cardiac output. Another echocardiography technique uses Doppler ultrasound to measure cardiac output. Echocardiographic measurement of the aortic root cross-sectional area (or, alternatively, the descending aorta area) is multiplied by the Doppler measured velocity-time integral of blood flow through that area combined with the heart rate to yield cardiac output. Again, these echocardiography techniques provide single measurements and cannot be easily adapted for continuous or instantaneous monitoring.
Echocardiography has other practical limitations. The ultrasound-imaging machines used in echocardiography are bulky, power hungry, expensive, and technically complex. They also require a skilled sonographer to hold and manipulate the gel-covered transducer while simultaneously optimizing settings. Additionally, ultrasound waves do not propagate well through either bone, such as the ribs or sternum, or air, resident in lungs, which can create an acoustic impediment to tracking heart motion. In fact, some patients cannot be ultrasonically imaged because of poor acoustic windows. Because of these limitations, echocardiography is typically limited to intermittent use in a hospital or clinical environment and has never been know to be used as a continuous, mobile long-term monitoring technique.
In addition to the above, various forms of cardiac catheterization may be used to assess a subject's cardiac health. However, cardiac catheterization is an extremely invasive, risky and expensive procedure. Catheterization actually requires the insertion of different sensors in the cardiac chambers. Due to its extremely invasive nature, cardiac catheterization can introduce a wide range of complications, including bleeding at the puncture site, cardiac arrhythmia, cardiac tamponade, vein or artery trauma, low blood pressure, infection, embolism from blood clots, allergic reaction, hemorrhage, stroke or death. Although cardiac catheterization can provide useful information concerning cardiovascular function, the associated risks posed make it undesirable for many patients. In fact, cardiac catheterization, in and of itself, can be a significant contributor to subject morbidity.
A first catheter-based method used to determine stroke volume is the “direct” Fick cardiac output technique. This technique is based on the principle that the difference in oxygen content across the lungs multiplied by the measured cardiac output should equal the total amount of oxygen transferred into the blood each minute. First, this approach requires the accurate measurement of the subject's total oxygen uptake from a bag, which the patient breathes from during the course of the test. Next, determining the oxygen difference across the lungs also requires obtaining invasive blood samples from the patient's systemic arteries and from the patient's vena cava or pulmonary arteries. These measurements require multiple medical personnel performing meticulous measurements and invasive sampling for a single snapshot determination of stroke volume. Multiple or serial determinations are not feasible.
A second catheter-based technique for obtaining cardiac data is the “indirect” Fick cardiac output method. Since the collection and accurate analysis of a large bag of expired gas is difficult, as required in the “direct” Fick methodology, the “indirect” Fick relies on an assumption of the average expected oxygen consumption. However, the indirect Fick still requires invasive sampling of arterial and venous blood with catheters to obtain the arterial venous oxygen difference. In addition, the assumption of oxygen consumption is very likely to introduce error in the final calculation of cardiac output. Additionally, as with the “direct” Fick method, given the need for significant personnel and lab requirements, this technique is only used in cardiac catheterization and research laboratories.
A third catheter-based technique is the indicator dilution method. In this approach, one injects a known amount of dye or thermal fluid into a subject's flowing blood stream. The dilution of the agent downstream from its injection point may be used as a measure of the volume that produced the dilution per unit of time. Again, as with other undesirable catheter approaches, this technique also requires invasive catheter access to both the central venous and arterial systems, with all its associated potential complications.
Indicator dilution methods using dyes are rarely performed today. Instead, modern approaches rely on thermal dilution techniques. Catheters are fitted with a distal heated filament, which allows automatic thermo-dilution measurement via heating the blood and measuring the resultant thermo-dilution trace. Due to associated negative impacts, dilution measurements cannot be performed too frequently, and, can be subject to error in the presence of certain muscle relaxants. The thermal dilution technique is currently used in catheterization laboratories and can be used to obtain serial measurements of cardiac output in patients with pulmonary artery catheters in acute care settings. However, as with other cardiac catheterization techniques, the invasive catheter requires trained personnel for placement and repeated injections. Although monitoring for days is possible, longer periods are associated with catheter related infections and other complications.
Impedance cardiography (ICG), also known as thoracic electrical bio-impedance, is an additional technology used to assess cardiac function. ICG works in conjunction with ECG, which creates a more complex application. ICG is based on associating measured changes in thoracic impedance to estimates of changes in thoracic volume. As with an ECG, ICG can only be used to indirectly track volumetric changes during the cardiac cycle. In practice, with an ICG, an alternating current is transmitted through a subject's chest. The current is expected to seek the path of least resistance, which is generally presumed to be the blood-filled aorta. However, other features such as lung congestion can affect this measurement. Baseline thoracic impedance to the impressed current is measured and then, the corresponding changes in impedance are used in conjunction with ECG to provide hemodynamic parameters. The technique requires careful placement of four neck and four chest electrodes, along with trained personnel and additional specialized equipment.
Generally, the type of cardiac monitoring used, whether intermittent or continuous, has been found to affect delivery of care. In a study of patients with low cardiac output states in a coronary care unit, cardiac output determined by using a continuous method was compared with cardiac output determined by using an intermittent method every 4 hours. It was shown that the method used to monitor cardiac output delivered data that directly affected delivery of care. Continuous measurement of cardiac output increased the number of treatment decisions and actions by healthcare providers and decreased the length of hospital stay by a median of 2 days.
An ideal system for measuring stroke volume and cardiac output would combine the best qualities of the previously described existing systems without the associated negative aspects. It would be desirable to provide a cardiac measuring system that can detect advanced cardiac functions, but is not invasive, does not require surgery, preferably does not even require any skin contact, conductive gels or electrode patches, is low power without any significant ionizing radiation, allows long-term continuous patient monitoring, is extremely safe, and is much more affordable than current techniques. The present invention is directed to overcoming, or at least reducing, the effects of one or more of the problems set forth above.